A recombinant dromedary antibody fragment (VHH or nanobody) directed against human Duffy antigen receptor for chemokines
2010
Smolarek, Dorota | Hattab, Claude | Hassanzadeh-Ghassabeh, Gholamreza | Cochet, Sylvie | Gutiérrez, Carlos | Brevern, Alexandre G. de | Udomsangpetch, Rachanee | Picot, Julien | Grodecka, Magdalena | Wasniowska, Kazimiera | Muyldermans, Serge | Colin, Yves | Le Van Kim, Caroline | Czerwiński, Marcin | Bertrand, Olivier
Fy blood group antigens are carried by the Duffy antigen receptor for chemokines (DARC), a red cells receptor for Plasmodium vivax broadly implicated in human health and diseases. Recombinant VHHs, or nanobodies, the smallest intact antigen binding fragment derivative from the heavy chain-only antibodies present in camelids, were prepared from a dromedary immunized against DARC N-terminal extracellular domain and selected for DARC binding. A described VHH, CA52, does recognize native DARC on cells. It inhibits P. vivax invasion of erythrocytes and displaces interleukin-8 bound to DARC. The targeted epitope overlaps the well-defined DARC Fy6 epitope. K D of CA52-DARC equilibrium is sub-nanomolar, hence ideal to develop diagnostic or therapeutic compounds. Immunocapture by immobilized CA52 yielded highly purified DARC from engineered K562 cells. This first report on a VHH with specificity for a red blood cell protein exemplifies VHHs' potentialities to target, to purify, and to modulate the function of cellular markers.
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